Undergraduate Awards – Highly Commended 2018

Congratulations to the following students and graduates who have been Highly Commended in the 2018 Undergraduate Awards.

These awards aim to celebrate top undergraduate coursework and foster interdisciplinary collaboration between students and recent graduates worldwide.

Professor Karl Leydecker, Vice-Principal (Learning and Teaching) said, “We are absolutely delighted that so many of our students have been named Highly Commended Entrants this year. This is a fantastic achievement. The Undergraduate Awards receive many thousands of submissions from over 40 countries, so it’s great to see University of Dundee students named in these prestigious awards that attract entries from some of the world’s top universities.”

Conscientisation through Story: An Impact Assessment of the Inside Outside Exhibition, developed by Women in Prostitution

This research examines the impact of an exhibition as part of the Inside Outside project, sharing the stories and experiences of women involved in prostitution through narrative storytelling. Using a mixed-methods approach, the research examined both the immediate and subsequent emotions, thoughts and actions of visitors. The report concludes that upon experiencing the exhibition, visitors developed a critical consciousness as they unpicked notions of individualism, victim blaming and a normalisation of male aggression and entitlement, while applying elements of their experience to the context of their own realities. It was argued that the exhibition encouraged individual action of visitors, however, a gap was identified in mobilising individuals towards collaborative transformative action. It is further suggested that Community Learning and Development practice recognise the important role that narrative storytelling can have in developing critical consciousness beyond the limits of group settings.

Characterizing the expression of glycans ligands for Siglec-E in normal mouse lung (Lung inflammation and how the immune system is able to keep the lungs calm and not over-react  unless there is something to attack)

Neutrophil recruitment into the lung is important in the defence against pathogens, but if uncontrolled can lead to lung inflammation and tissue damage. Sialic acid binding immunoglobulin-like lectin-E (Siglec-E) is a negative immune regulator constitutively expressed on neutrophil membranes. Siglec-E has been implicated in suppressing neutrophil recruitment through binding to sialic acid containing glycoproteins on lung endothelial cells. In this study, we investigated Siglec-E binding activities to mouse lung cells. Recombinant Siglec-E human IgG1 Fc (Siglec-E-Fc) was multimerized on protein A nanobeads, and the binding to the cells were measured by flow cytometry. Cell populations were identified by markers for endothelial cells (CD31), leukocytes (CD45), alveolar macrophages (CD170) and epithelial cells (CD326) with control samples treated with sialidase to remove sialic acid. The data showed lung endothelial cells, epithelial cells and leukocytes exhibited a distinct binding patterns and binding was inhibited by sialidase treatment of the cells. Additionally, Siglec-E counter-receptors on endothelial cells were characterized. Lung endothelial cells were isolated by magnetic activated cell sorting. The counter-receptors were selectively biotinylated by a recently developed proximity labelling method. Biotinylation of discrete proteins were consistently detected by Streptavidin-HRP Western blot. The identification of these proteins will require quantitative proteomics. These data demonstrate that endothelial cells expressed ligands for Siglec-E, consistent for inhibiting neutrophil recruitment.

For non biologists:

How does your body know when bugs get inside and invade us? The truth is sugar coated… literally. All cells, your own or those invading, are coated in sugar chains. These decorate your cells with a dense coating like a forest. Your body’s immune system can taste the difference. A little detector called a Siglec is able to taste these sugars. By tasting the outer leaves in the forest, the Siglec can then report back either good (healthy) or bad (infected) news.

The neutrophil is like a bodyguard, a white blood cell that can respond quickly and attack invaders. Neutrophils carry Siglec-E to taste our own sugars and this is important to keep lungs healthy and calm. If Siglec-E is missing, the lungs can get very irritated. Lung inflammation can sometimes be fatal.

The aim of this work was to see which cells are decorated with the sugars that Siglec-E can taste. We tested different cells from the lung, and Siglec-E could recognise sugars on the cells that line the blood stream, endothelial cells. This makes sense as neutrophils flow through the blood until they are needed elsewhere in the body. We also aimed to identify where are these sugar chains are rooted to our healthy endothelial cells. We used a new experiment to find out. We let the Siglec-E taste the sugars on endothelial cells and then sprayed everything nearby to find out. These results could help treat lung inflammation in the future by paving the way to develop new medicines.

Essay question: “The blind live in a world built by and for the sighted” (Butler, 1994, p.368). Examine this statement with regard to the shift from a ‘medical’ to a ‘social’ model and, more recently, and ’embodied’ model, of disability.”

The influence of novel antidepressants on hippocampal excitatory neurotransmission

Current antidepressant therapies require weeks to improve mood in some patients and most current therapeutics act by inhibiting transporters for serotonin and noradrenaline. Recently, the rapid antidepressant effects of ketamine were proposed to be mediated by a metabolite, which facilitates AMPA receptor (AMPAR) function, encouraging research into developing AMPAR enhancers as rapidly-acting antidepressants. The effects of the putative antidepressant CX614, the clinically used atypical antidepressant tianeptine, the ketamine metabolite 2R,6R-HNK and naloxone on hippocampal excitatory neurotransmission were compared. An electrophysiological technique on mouse hippocampal brain slices was used to record the field excitatory postsynaptic potential (fEPSP) from CA1 pyramidal neurons, which results from glutamate activation of dendritic AMPARs, in response to Schaffer collateral stimulation. CX614 (10mM) primarily prolonged the fEPSP decay time (p<0.05), suggesting an action to reduce AMPAR desensitisation, or prolong deactivation. By contrast, tianeptine (10 mM) primarily increased the fEPSP peak amplitude and slope (p<0.05), suggesting an increase in active synaptic AMPARs. Both tianeptine and naloxone are known to phosphorylate the AMPAR GluA1 subunit. However, naloxone (10 mM) had no effect on the fEPSP, suggesting GluA1 phosphorylation is not required for the effects of tianeptine on AMPARs. The host laboratory demonstrated that 2R,6R-HNK (10 mM) greatly enhanced the function of synaptic AMPARs located close to the CA1 cell body. Surprisingly, 2R,6R-HNK (30 mM) only had a very modest effect on the dendritic fEPSP decay time, suggesting a distribution of different AMPAR isoforms depending on location. In conclusion, tianeptine and CX614 enhance dendritic AMPAR function, but by different mechanisms.

Completed in Professor Jeremy Lambert’s lab in the Division of Neuroscience at Ninewells Hospital, with the support from both Professor Lambert and Dr Olivia Monteiro.

For non biologists:

Current antidepressant therapies require weeks to improve mood in some patients and most current therapeutics act by inhibiting transporters for serotonin and noradrenaline. These are often termed the ‘happy’ chemicals in the brain, so blocking the recycling of these chemicals will keep their concentration high for an ideally positive effect. These chemicals travel from one brain cell (neuron) to the next across the synapse, which is the area between two neurons. Recently, the rapid antidepressant effects of ketamine were proposed to be mediated by a metabolite, which facilitates the function of a receptor on the cell surface known as the AMPA receptor (AMPAR). Cell receptors can allow chemicals to pass in and out of cells, so this has encouraged research to aim at developing AMPAR enhancers as rapidly-acting antidepressants. The effects of the putative antidepressant CX614, the clinically used atypical antidepressant tianeptine, the ketamine metabolite 2R,6R-HNK and naloxone were compared. These four chemicals were examined for their effect on the chemical signals in the hippocampus part of the brain. A laboratory technique called electrophysiology was used on mouse hippocampal brain slices. This technique could record a type of signal called the field excitatory postsynaptic potential (fEPSP) which was formed by another chemical in the brain called glutamate, that activated the AMPARs. These signals were recorded from specific brain cells (CA1 pyramidal neurons) after one of the electrodes in this technique stimulated a signal pathway in the hippocampus called Schaffer collateral stimulation. Different aspects of the fEPSP signal were examined like the slope, decay time and peak which suggested how the different compounds were working. CX614 (10mM) primarily prolonged the fEPSP decay time (p<0.05), suggesting an action to reduce AMPAR desensitisation, or prolong deactivation. This means the AMPARs were thought to be open for longer, increasing the neuronal signals. By contrast, tianeptine (10 mM) primarily increased the fEPSP peak amplitude and slope (p<0.05), suggesting an increase in the number of active synaptic AMPARs. Both tianeptine and naloxone are known to modify part of the AMPAR which is the GluA1 subunit. It does this through a process of adding on a chemical group called phosphoryl through phosphorylation. However, naloxone (10 mM) had no effect on the fEPSP, suggesting GluA1 phosphorylation is not required for the effects of tianeptine on AMPARs. The host laboratory demonstrated that 2R,6R-HNK (10 mM) greatly enhanced the function of synaptic AMPARs located close to the CA1 cell body. Surprisingly, 2R,6R-HNK (30 mM) only had a very modest effect on the dendritic fEPSP decay time, so did not hugely alter the time the receptors were open. The dendrites are located further away from the cell body, suggesting a distribution of different AMPAR isoforms depending on location. In conclusion, tianeptine and CX614 enhance dendritic AMPAR function, increasing the signals recorded but by different mechanisms. This has uncovered some of the different approaches that antidepressant therapies may work through.

Ireland and Colonialism

Ireland and Colonialism is an essay that addresses the conflict caused by English imperialism in Ireland, but more particularly examines the additional tensions that arose from the shared ethnic, religious and political histories that were created during these centuries of English rule. From an English perspective, then, theirs was often an encounter with the ‘imperfect Otherness’ of the Irish, and these conflated relationships created a problem of proximity encapsulated within the resultant Anglo-Irish identity. This paper therefore examines the dilemma of this hybrid (and hyphenated) cultural identity, through the lens of two essentially political works by the Anglo-Irish authors Jonathan Swift, The Story of the Injured Lady (1707) and Maria Edgeworth’s Castle Rackrent (1800).

Fragments for Fungi: Biochemical and Structural Characterisation of Potential AfGNA1 Inhibitors Towards the Development of Novel Antifungal Compounds

Aspergillus fumigatus is a fungi which can cause a fatal infection by colonising the lung upon inhalation. Immuno-compromised individuals , such as those with HIV, cancer or undergoing transplantation, are most at risk, yet current treatments for the disease are ineffective or have harmful side-effects. Therefore, there is an unmet clinical need for new drugs which tackle this disease.

Genetics experiments carried out by the Van Aalten lab revealed that the Aspergillus fumigatus protein ‘GNA1’ is essential to the survival of the fungi. GNA1 contributes to the development of the fungal cell wall; therefore GNA1 may be a promising new drug target for this disease.

Structural studies using X-ray crystallography identified a small molecule which binds tightly to GNA1. This molecule could be modified to generate an inhibitor of the protein. Using iterative chemical synthesis and optimisation cycles, a new molecule was developed from the original compound which extends into the GNA1 active site. Whilst this new molecule does not inhibit GNA1, it is thought that further optimisation of this compound could lead to the development of a GNA1 inhibitor: the first step towards drug discovery.

Documentary Photography as a Phenomenological Lens: Into the Lifeworld of the Prison

Drawing upon case studies from various documentary photography projects within prisons, this essay explores the idea that this ‘prison photography’ could act as a mode of phenomenological sight. Taking into account the wider political context of this, it assesses the potential for these projects to disrupt the elements of the carceral system which contribute to the creation of a ‘secret’ lifeworld’ – a defining characteristic of the prison system. This essay concludes that agency in the image-creation process is central to prison photography acting as phenomenological sight, and that this opens up many potentials for prison photography to be a starting point for wider conversations.